3篇
您的检索式：作者名="Lianghe Mei"
|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Inhibiting Hv1 channel in peripheral sensory neurons attenuates chronic inflammatory pain and opioid side effects显示文摘Both opioids and nonsteroidal anti-inflammatory drugs(NSAIDS)produce deleterious side effects and fail to provide sustained relief in patients with chronic inflammatory pain.Peripheral neuroinflammation(PN)is critical for initiation and development of inflammatory pain.A better understanding of molecular mechanisms underlying PN would facilitate the discovery of new analgesic targets and the development of new therapeutics.Emerging evidence suggests that peripheral sensory neurons are not only responders to painful stimuli,but are also actively engaged in inflammation and immunity,whereas the intrinsic regulatory mechanism is poorly understood.Here we report the expression of proton-selective ion channel Hv1 in peripheral sensory neurons in rodents and humans,which was previously shown as selectively expressed in microglia in mammalian central nervous system.Neuronal Hv1 was up-regulated by PN or depolarizing stimulation,which in turn aggravates inflammation and nociception.Inhibiting neuronal Hv1 genetically or by a newly discovered selective inhibitor YHV98-4 reduced intracellular alkalization and ROS production in inflammatory pain,mitigated the imbalance in downstream SHP-1-pAKT signaling,and also diminished pro-inflammatory chemokine release to alleviate nociception and morphine-induced hyperalgesia and tolerance.Thus,our data reveal neuronal Hv1 as a novel target in analgesia strategy and managing opioids-related side effects. | Qiansen Zhang Yimin Ren Yiqing Mo Peipei Guo Ping Liao Yuncheng Luo Jie Mu Zhuo Chen Yang Zhang Ya Li Linghui Yang Daqing Liao Jie Fu Juwen Shen Wei Huang Xuewen Xu Yanyan Guo Lianghe Mei Yunxia Zuo Jin Liu Huaiyu Yang Ruotian Jiang | 2022 | Cell Research2022，32，5： | 3 |
| 2 | Molecular basis for ligand activation of the human KCNQ2 channel显示文摘The voltage-gated potassium channel KCNQ2 is responsible for M-current in neurons and is an important drug target to treat epilepsy,pain and several other diseases related to neuronal hyper-excitability.A list of synthetic compounds have been developed to directly activate KCNQ2,yet our knowledge of their activation mechanism is limited,due to lack of high-resolution structures.Here,we report cryo-electron microscopy(cryo-EM)structures of the human KCNQ2 determined in apo state and in complex with two activators,ztz240 or retigabine,which activate KCNQ2 through different mechanisms.The activator-bound structures,along with electrophysiology analysis,reveal that ztz240 binds at the voltage-sensing domain and directly stabilizes it at the activated state,whereas retigabine binds at the pore domain and activates the channel by an allosteric modulation.By accurately defining ligand-binding sites,these KCNQ2 structures not only reveal different ligand recognition and activation mechanisms,but also provide a structural basis for drug optimization and design. | Xiaoxiao Li Qiansen Zhangc Peipei Guo Jie Fu Lianghe Mei Dashuai Lv Jiangqin Wang Dongwu Lai Sheng Ye Huaiyu Yang Jiangtao Guo | 2021 | Cell Research2021，31，1： | 3 |
| 3 | Transarterial infusion chemotherapy with FOLFOX for advanced hepatocellular carcinoma:a multi-center propensity score matched analysis of real-world practice显示文摘Background:To compare the treatment effectiveness and safety among transarterial infusion chemotherapy(TAI)with FOLFOX regimen,transarterial chemoembolization(TACE),and sorafenib in patients with BCLC stage C hepatocellular carcinoma(HCC).Methods:The data of consecutive patients with BCLC stage C HCC treated with TAI,TACE,or sorafenib from January 2015 to December 2018 at three centers were retrospectively analyzed.Propensity-score matched(PSM)analysis was pairwise performed to reduce selection bias.Treatment effectiveness and safety were evaluated and compared using the Kaplan-Meier method,log-rank test,Cox regression models,andχ2 test.Results:The median overall survival(OS)in the matched TAI cohort was significantly longer than the sorafenib cohort(19.6 vs.7.5 months,P=0.009),and the TACE cohort(estimated 27.8 vs.6.6 months,P<0.001).The difference in median progression-free survival(PFS)between the matched TAI and sorafenib cohorts was not significant(5.8 vs.2.3 months,P=0.219).The median PFS in the matched TAI cohort was significantly longer than the TACE cohort(6.5 vs.2.8 months,P<0.001).The objective response rate(ORR)in the matched TAI cohort was significantly higher than the sorafenib cohort(36.4%vs.0.0%,P<0.001)and the TACE cohort(48.7%vs.4.7%,P<0.001).The incidences of adverse events(AEs)were similar among these three cohorts.Conclusions:TAI with FOLFOX regimen was an effective and safe therapy that improved survival of patients with BCLC stage C HCC. | Shaohua Li Jie Mei Qiaoxuan Wang Feng Shi Hongyan Liu Ming Zhao Lianghe Lu Yihong Ling Zhixing Guo Yabing Guo Xiaoming Chen Ming Shi Wan Yee Lau Wei Wei Rongping Guo | 2021 | Hepatobiliary Surgery and Nutrition2021，10，5： | 2 |
您所在的机构暂未开通此部分的功能，请联系管理员